98 articles - From Friday Jul 08 2022 to Friday Jul 15 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations prior to clinical progression, and in screening asymptomatic people for cancer. Recommendation for reporting of results, future development of ctDNA assays, and future clinical research are made. |
meta-analyses and systematic reviews
| Blood Adv |
Comparative efficacy and tolerability of novel agents vs chemotherapy in relapsed and refractory T-cell lymphomas: a meta-analysis. Our results highlight SA as an attractive outpatient option for R/R PTCL, and their incorporation in the development of upfront treatment paradigms merits urgent consideration. Our results underscore enrollment in clinical trials of SA as a critical strategy for R/R PTCL. |
Interaction of von Willebrand factor with blood cells in flow models: a systematic review. This review might provide a starting point for future research. Extended knowledge on the influence of blood flow on VWF and blood cell interactions can contribute to improved understanding of the variation in bleeding in patients with bleeding disorders. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Developmental changes in iron metabolism and erythropoiesis in mice with human gain-of-function erythropoietin receptor. In conclusion, the erythroid drive which initially inhibits hepcidin production in mtHEPOR mice in the prenatal/perinatal period is postnatally abrogated by increasing iron stores promoting hepcidin synthesis. The differences observed in studied characteristics between mtHEPOR heterozygotes and homozygotes suggest dose-dependent alterations of downstream EPOR stimulation. |
The pleiotropic effects of alpha thalassemia on HbSS and HbSC sickle cell disease: reduced erythrocyte cation co-transport activity, serum erythropoietin, and transfusion burden, do not translate into increased survival. Finally, in a larger cohort we report a median survival of 62yrs in patients with HbSS (n=899) and 80yrs in those with HbSC (n=240). a-thalassemia did not influence survival in HbSS, but a non-significant trend was seen in those with HbSC. |
| Blood |
Combined single-cell tracking and omics improves blood stem cell fate regulator identification. Their identities, kinship and histories are maintained throughout, massively improving molecular noise filtering and candidate identification. In addition to many identified blood stem CFD regulators, we here provide this pipeline for use also in CFDs other than asymmetric division. |
Developing a Classification of Hematologic Neoplasms in the Era of Precision Medicine. A collaborative clinico-pathologic review process will provide a mechanism to update pathologic and genomic criteria within a clinical context. An interactive web-based portal would make the classification more immediately available to the scientific community, while providing accessory features enabling practical application of diagnostic, prognostic, and predictive information. |
Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update which includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations. |
Grab regulates transferrin receptor recycling and iron uptake in developing erythroblasts. Mechanistically, Grab regulates the exocytosis of Tfrc-associated vesicles by activating the GTPase Rab8, which subsequently promotes the recruitment of the exocyst complex and vesicle exocytosis. Our results reveal a critical role for Grab in regulating the Tf cycle and provide new insights into iron homeostasis and erythropoiesis. |
Immune landscape after allo-HSCT: TIGIT and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 post-HSCT were distinct features significantly associated with subsequent AML relapse in a second cross sectional cohort. Altogether, these data provide global insights into the immunoregulatory landscape reconstitution following HSCT, and highlight non-canonical inhibitory receptors associated with relapse, which could open the path towards new prognostic tools or therapeutic targets to restore subverted anti-AML immunity. |
Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey. Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or non-definitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by CNB. |
Next-generation ALK inhibitors are highly active in ALK-positive large B-cell lymphoma. One with progressive disease was treated with lorlatinib and achieved complete response. These data support use of alectinib and lorlatinib as off-label therapeutic options for patients with relapsed or refractory ALK-positive large B-cell lymphoma. |
Race, Rituximab, and Relapse in TTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression following rituximab treatment. How race, racism, and the social determinants of health contribute to the disparity in relapse risk in iTTP deserve further study. |
| Blood Adv |
BMX Kinase Mediates Gilteritinib Resistance in FLT3-mutated AML through Microenvironmental Factors. Subsequent gene module analyses indicated that gilteritinib responsiveness was associated with lymphocyte differentiation and myeloid leukocyte activation, whereas unresponsiveness to gilteritinib was associated with upregulation of cell-cycle, DNA/RNA metabolic processes, and protein translation. Collectively, these findings indicate a crucial role for microenvironment-mediated factors modulated by BMX in the escape from targeted therapy and have implications for the development of novel therapeutic interventions to restore sensitivity to gilteritinib. |
Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency. There was loss of plasma membrane VWF in RUNX1- and RAB31- deficient megakaryocytic HEL cells, and RHD-iMKs These studies provide evidence that RAB31 is downregulated in RUNX1 haplodeficiency and regulates megakaryocytic vesicle trafficking of 3 major proteins with diverse biological roles. Early endosome defect and impaired vesicle trafficking is a potential mechanism for the |
Differences in wild type- and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338L-FIX activity in patients after gene therapy. |
Disparities in trial enrollment and outcomes of Hispanic adolescent and young adult acute lymphoblastic leukemia. In summary, Hispanic patients treated on CALGB 10403 did as well as NHWs and better than population estimates. Geographical misalignment between trial sites and disease epidemiology may partially explain the lower-than-expected enrollment of Hispanic AYA ALL patients. |
Efflux Capacity and Aldehyde Dehydrogenase Both Contribute to CD8+ T-cell Resistance to Posttransplant Cyclophosphamide. Yet, MHC-mismatched murine HCT studies revealed that peripherally expanded, phenotypically memory T cells 1-3 months post-transplant originated largely from naïve-derived rather than memory-derived T cells surviving PTCy, suggesting that initial resistance and subsequent immune reconstitution are distinct. These studies provide insight into the complex immune mechanisms active in CD8+ T-cell survival, differentiation, and reconstitution after cyclophosphamide, with relevance for post-HCT immune recovery, chemotherapy use in autologous settings, and adoptive cellular therapies. |
Extended Duration Letermovir Prophylaxis for Cytomegalovirus Infection after Cord Blood Transplantation in Adults. Letermovir is highly effective, well tolerated prophylaxis that mitigates CMV infection, CMV-related mortality and antiviral therapy toxicities in CBT recipients. Our data supports prophylaxis duration of at least 6 months after CBT. |
Genomic and microenvironmental landscape of stage I follicular lymphoma, compared to stage III/IV. This exploratory study shows that FL stage I is genetically heterogenous with different underlying oncogenic pathways. Stage I FL BCL2trl- is likely STAT6 driven while BCL2trl- stage III/IV appears to be more BCL6trl driven. |
HMGA2 expression defines a subset of AML with immature transcriptional signature and vulnerability to G2/M inhibition. Accordingly, small molecules that target G2/M proteins were preferentially active in vitro and in vivo on HMGA2+ AML specimens. Together, our findings suggest that HMGA2 is a key functional determinant in AML and is associated with stem cell features, G2/M status and related drug sensitivity. |
Impaired microtubule dynamics contribute to microthrombocytopenia in RhoB-deficient mice. Our findings imply that the reduction of this tubulin posttranslational modification results in impaired microtubule dynamics, which might contribute to microthrombocytopenia in RhoB-deficient mice. Importantly, we demonstrate that RhoA and RhoB are localized differently and have selective, non-redundant functions in the megakaryocyte lineage. |
Incidence and Predictors of Priapism Events in a Sickle Cell Anemia: A Diary-Based Analysis. Major priapism occurred in 9.9% of episodes and was associated with the sum of future priapism events. Men with SCA and at least 3 priapism episodes in the past 12 months are at significant risk for recurrent priapism in the following 3 months. |
Inflammation accelerates BCR-ABL1+ B-ALL development through upregulation of AID. The heat shock protein 90 (Hsp90) inhibitors significantly reduce AID protein level and delay the disease progression of BCR-ABL1+ B-ALL upon inflammatory stimulation. The present data demonstrate the causative role of AID in the development and progression of BCR-ABL1+ B-ALL during inflammation, thus highlighting potential therapeutic targets. |
Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA. Importantly, the therapeutic efficacy of a single dose of the CD3/BCMA BsAb was remarkably augmented by restoring iNKT cell activity using adoptive transfer of a-galactosylceramide-loaded DCs. Together, these results reveal iNKT cells as a critical player for the anti-tumor activity of CD3-engaging BsAbs, providing important translational implications. |
Low Incidence of Invasive Fungal Disease Following CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Non-Hodgkin Lymphoma. IFD was rare amongst patients who received CD19 CAR-T therapy for NHL in the absence of routine antifungal prophylaxis despite frequent toxicities including CRS, ICANS, and late neutropenia. This study suggests that in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated. |
MiR-146b-5p regulates il-23 receptor complex expression in chronic lymphocytic leukemia cells. Our findings indicate that IL-12ß1 expression, a crucial checkpoint for the functioning of the IL-23/IL-23R complex loop, is under the control of miR-146b-5p, which may represent a potential target for therapy since it contributes to the CLL pathogenesis. This trial is registered at as NCT00917540. |
Neighborhood disadvantage, health status, and healthcare utilization after blood or marrow transplant: BMTSS report. In BMT survivors, access to healthcare and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors. |
NK cell CD56bright and CD56dim subset cytokine loss and exhaustion is associated with impaired survival in myeloma. These results suggest that NK cell exhaustion is already present by the time of myeloma diagnosis and likely contributes to the loss of immunological control of malignant plasma cells. Restoring NK cell function via immune directed therapies offers a route to restoring immunological control in multiple myeloma. |
Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Fusions Associated with Ph-like ALL. Relapse rate was associated with disease status (P=0.028) and conditioning regimen intensity (P=0.028). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL. |
Real world study of children and young adults with myeloproliferative neoplasms identifying risks and unmet needs. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN. |
Third-party CMV- and EBV-specific T cells for first viral reactivation after allogeneic stem cell transplant. Early administration of third-party VST in conjunction with antiviral treatment appears safe and leads to excellent viral control and clinical outcomes. Study ID ACTRN12618000343202. |
Total marrow and lymphoid irradiation as conditioning in haploidentical transplant with posttransplant cyclophosphamide. For patients treated with 2000 cGy, with a median follow-up duration of 12.3 months, 1-year relapse/progression, progression-free survival, and overall survival rates were 17%, 74%, and 83%, respectively. In conclusion, HaploHCT-TMLI with PTCy was safe and feasible in our high-risk patient population with promising outcomes. |
Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies by augmenting tumor cell phagocytosis. Mechanistically, double-hit lymphoma cells subjected to VEN triggered phagocytosis in an apoptosis-independent manner. Our study identifies the combination of VEN and therapeutic antibodies as a promising novel strategy for the treatment of B-cell malignancies. |
| Blood Cancer J |
A scoring system for AML patients aged 70 years or older, eligible for intensive chemotherapy: a study based on a large European data set using the DATAML, SAL, and PETHEMA registries. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n |
Therapy-related clonal cytopenia as a precursor to therapy-related myeloid neoplasms. The presence of cytogenetic abnormality and the absence of variants in DNMT3A, TET2, or ASXL1 (DTA-genes) were associated with a higher likelihood of developing a subsequent t-MN and an inferior survival. We describe a putative precursor entity of t-MN with distinct features and outcomes. |
| CA Cancer J Clin |
Health insurance status and cancer stage at diagnosis and survival in the United States. Patients without private insurance coverage had worse short-term and long-term survival at each stage for al cancers combined; patients who were uninsured had worse stage-specific survival for 12 of 17 stageable cancers and had worse survival for leukemia and brain tumors. Expanding access to comprehensive health insurance coverage is crucial for improving access to cancer care and outcomes, including stage at diagnosis and survival. |
| Haematologica |
Improved outcomes with 7+3 induction chemotherapy for acute myeloid leukemia over the past four decades: analysis of SWOG trial data. The relative benefit associated with CR1 and the relative detriment associated with relapse have decreased over this period; while achieving CR1 and relapse from CR1 still have strong prognostic associations with outcomes, the magnitude of the association has decreased over time. Possible explanations for these patterns include higher CR rates with salvage therapies after relapse, more frequent use of hematopoietic cell transplant, and better supportive care. |
PDL1 shapes the classical Hodgkin lymphoma microenvironment without inducing T cell exhaustion. Instead, we identified a strong association between PDL1 expression and CHL MHC-II expression, TH recruitment, and enrichment of Th1 regulatory cells. These data suggest that a dominant effect of PDL1 expression in CHL may be T helper engagement and promotion of regulatory microenvironment rather than maintenance of exhaustion. |
RHOA regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia. This elevated IGFBP2 expression is confirmed in primary CML samples. Thus, we demonstrate one mechanism whereby RHOA-SRF-IGFBP2 signaling axis contributes to development of leukemia in cells expressing the p210 BCRABL1 fusion kinase. |
| J Hematol Oncol |
Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis. This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer. |
| Leukemia |
APR-246 triggers ferritinophagy and ferroptosis of diffuse large B-cell lymphoma cells with distinct TP53 mutations. TP53 mutations on exons 5, 6 and 7 are predictors of progression and survival. Targeting mutant p53 by APR-246 is a promising therapeutic approach for DLBCL patients. |
GFI1B acts as a metabolic regulator in hematopoiesis and acute myeloid leukemia. FAO or OXPHOS inhibition significantly impeded leukemia progression of Gfi1b-KO MLL/AF9 cells. Finally, we showed that Gfi1b-deficient AML cells were more sensitive to metformin as well as drugs implicated in OXPHOS and FAO inhibition, opening new potential therapeutic strategies. |
| Thromb Haemost |
Bleeding propensity in Waldenström Macroglobulinaemia: Potential causes and evaluation. It is thus important to understand the origin of the WM bleeding phenotype to better stratify patients according to their bleeding risk and thus enhance confidence in clinical decisions regarding treatment management. In this review, we detail the evidence for various contributing factors to the bleeding phenotype in WM and focus on current and emerging diagnostic tools that will aid evaluation and management of bleeding in these patients. |
CLEC-2 supports platelet aggregation in mouse but not human blood at arterial shear. The reduction in platelet aggregation observed in CLEC1bfl/flGPIb-Cre+ mice during arterial thrombosis is mediated by the loss of CLEC-2 on mouse platelets. In contrast, CLEC-2 does not support thrombus generation on collagen, atherosclerotic plaque or inflamed endothelial cells in human at arterial shear. |
Does Fibrinolytic Strategy of Pulmonary Embolism International THrOmbolysis (PEITHO)-3 Trial Need More Strong Evidence? Major cardiovascular guidelines regarding PE have considered full-dose systemic fibrinolysis as Class 3 indication for submassive PE. Various alternative strategies have been designed to reduce bleeding complications without loss of efficacy. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis. Exploring the physiological consequences of disease chronicity unique to myelofibrosis, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for myelofibrosis transplantation. |
| Blood |
| J Hematol Oncol |
A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase. Lastly, as new treatment approaches continue to be explored in CML, this review also discusses the advent of newer therapies such as asciminib. This article may be a useful reference for physicians treating patients with CML with second-generation TKIs and, as it is focused on the physicians' international and personal experiences, may give insight into alternative approaches not previously considered. |
Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy. Given the synergistic effect of VEGFR and other therapies in tumor development and progression, VEGFR dual-target inhibitors are becoming an attractive approach due to their favorable pharmacodynamics, low toxicity, and anti-resistant effects. This perspective provides an overview of the development of VEGFR dual-target inhibitors from multiple aspects, including rational target combinations, drug discovery strategies, structure-activity relationships and future directions. |
Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy. |
Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53-MDM2 interaction. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| J Hematol Oncol |
First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML. |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |